Mesoporous Silica Nanoparticles Doped with Gold Nanoparticles for Combined Cancer Immunotherapy and Photothermal Therapy

Abstract

Cancer immunotherapy is a treatment that utilizes the host immune system to fight against cancer. Inducing a cancer antigenspecific adaptive immune response is key in cancer immunotherapy. Although diverse immune cells including dendritic cells (DCs) and T cells infiltrate a tumor, the activation of such immune cells is inhibited, owing to an immunosuppressive tumor microenvironment. In this study, we propose mesoporous silica nanoparticles (XL-MSNs) decorated with gold nanoparticles (Au@XL-MSNs) for the delivery of a high amount of CpG-ODNs to the tumor site to activate DCs infiltrated within the tumor for the induction of an antigen-specific adaptive immune response. During an in vitro test, CpG-ODNs delivered using Au@XL-MSNs were shown to be more effectively internalized by bone-marrow-derived dendritic cells (BMDCs), resulting in an enhanced expression of costimulatory molecules and an increased secretion of pro-inflammatory cytokines compared to soluble CpG-ODNs. Furthermore, an in vivo test demonstrated a more significant tumor growth inhibition and an enhanced survival rate result from the intratumoral injection of Au@XL-MSN-CpG compared to that treated using soluble CpG-ODNs. Furthermore, through the induction of a photothermal effect based on the assembled AuNPs on XL-MSNs, an enhancement of the cancer immunotherapy was achieved by generating a cancer antigen at the tumor site, which can be processed by tumor-infiltrated DCs. These findings suggest that our approach can be applied as a synergistic platform for efficient cancer immunotherapy, enabling a delivery of immunostimulating signals as well as in situ antigen generation through a photothermal effect.

Nanoparticles as Smart Carriers for Enhanced Cancer Immunotherapy

“…Moreover, these NPs decreased the intracellular glutathione (GSH) level and increased the ROS (reactive oxygen species) level which further induced strong cytotoxic T cell (CD8 + T cell) response as well as enhanced antitumor activity. In another study, Ong et al ( 2019 ) decorated extra-large porous MSNs with small GNPs for effective delivery of CpG-ODNs into DCs. They showed that delivery of CpG-ODNs using such nanoplatform enhanced the expression of co-stimulatory molecules as well as increased the secretion of pro-inflammatory cytokines (IL-12 and TNF-α) as compared to soluble CpG-ODNs in vitro .…”

A red light‐activable MnI(CO)3‐functionalized gold nanocomposite as the anticancer prodrug with theranostic potential

“…We also compare the cell viability data with the other gold nanoparticle hybrid and showed that 1-AuNPs remained nontoxic to the A549 cells in the dark, but in the presence of red light, it exhibited optimal toxicity (Table S7). [81][82][83][84][85][86][87][88] The IC 50 value of complex 1 was determined to be 89.0 and 39.2 μM in dark and red light, respectively ( Figure S36).…”

Emerging Strategies in Anticancer Combination Therapy Employing Silica‐Based Nanosystems

“…Apart from the combination of immunostimulants, Kim and co‐workers also explored the potential of combined immunotherapy plus PTT. [ 76 ] To do so, the authors have employed large pore MSNs to load small AuNPs (1−2 nm) suitable for PTE. Finally, to complete the system, the loaded AuNPs were functionalized with thiol‐modified CpG and PEG moieties to add the desired immunostimulant feature and to provide enough colloidal stability.…”